1. 3. Urology-Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Focal segmental glomerulosclerosis (fsgs), the most common primary glomerular disease, is a diverse clinical entity that arises after podocyte injury. although numerus studies suggested molecular pathways responsible for development of fsgs, many unknowns about its pathogenic mechanism is still remained. the present study investigated and confirmed the role of two important pathways that were predicted as candidates for pathogenesis of fsgs in our previous in silico analysis.
The expression level of four enzyme genes that were representative of “chondroitin sulfate degradation” and “eicosanoid metabolism”pathways were investigated in the urinary sediment of biopsy proven fsgs patients (n = 20) and healthy subjects (n=17) using quantitative real time polymerase chain reaction (q-rt-pcr). these target genes were arylsulfatase, hexosaminidase, cyclooxygenase-2 and prostaglandin i2 synthase. mann–whitney u test was used to compare different variables between patient and control groups, patients with proteinuria of > 3 gr/day and < 3gr/day, as well as patients with egfr > 60 ml/min/1.73 m2 and < 60 ml/min/1.73 m2. correlation of target genes and clinical and pathological characteristics of the disease was calculated. receiver operating characteristic (roc) analysis was performed to to assess and compare the diagnostic accuracy of gene expression level between the study groups. combination of target genes as a diagnostic or prognostic panel for roc analysis was carried out using multiple logistic regression.
The roc analysis revealed that combination of three target genes (i.e. hexosaminidase, arylsulphathase and cyclooxygenase-2) improve the diagnosis accuracy of patients group to 76%, however, the mean difference between healthy and patients groups was not significant. the expression level of prostaglandin i2 synthase was lowers the limit of rt-pcr detection. hexosaminidase were correlated with the level of proteinuria where cyclooxygenase-2 were correlated with interstitial inflammation and the serum creatinine level in the disease group. a combined panel of these three target genes improved the discriminant accuracy of disease progression in terms of proteinuria and glomerular filtration rate to 87% and 74% respectively.
Our data indicated that these target genes contributes in the pathogenesis of fsgs and can be considered as biomarkers for non-invasive evaluation of disease progression.
Focal segmental glomerulosclerosis, molecular pathway, biomarker, chondroitin sulfate, eicosanoid me